The broad objectives of the Gene Knockout Core (GKC) are to: (i) provide collaborative support for long-term efforts to model contraception strategies in knockout mice; and (ii) facilitate experiments to test hypotheses about the function of specific genes in spermatogenesis and fertilization. These objectives will be accomplished by constructing knockout mice for Center Grant investigators and assisting with their maintenance and analysis. The knockout or knock-in mouse approach is an excellent model system for the study of complex biological phenomena such as fertilization. Genes can now be routinely ablated in the mouse genome to determine the phenotypic effects of null mutations. In many cases, this experimental strategy can provide crucial clues concerning the potential function(s) of new genes. For example, ablation of a gene postulated to play a critical role in spermatogenesis or fertilization should result in homozygous null mice with a sterile phenotype if the hypothesis is correct. If fertile mice are generated, this indicates that the gene is either not critical for spermatogenesis or fertilization or has a redundant function. The goal of the GKC is to support efforts to characterize genes involved in reproduction. Ultimately, as new gene knockout models are developed, important biological information is expected to emerge from these studies which will directly impact our understanding of human reproduction. In addition, the results of these studies will play an important role in directing translational research toward genes that have the most potential utility as contraception targets.